We are investigating the regulation of spectrin phosphorylation in the human erythrocyte membrane. Spectrin is a major protein of the RBC membrane disposed in a fibrillar array on the inner surface of the membrane. Much evidence implicates spectrin in the maintenance of RBC shape and membrane deformability. Spectrin is composed of 2 peptide chains (MW 240,000 and 215,000). The lighter chain is phosphorylated by kinases located within the membrane. We are examining the regulation of these kinases, the sites on spectrin band 2 which are phosphorylated and the relationship of band 2 phosphorylation to membrane shape. Recent studies indicate that spectrin kinase is distinct from the cAMP-dependent protein kinase, and is not regulated by cyclic nucleotides. Spectrin kinase also phosphorylates band 3, the major transmembrane is distinct from spectrin. In our studies, RBC membrane shape and the degree of spectrin phosphorylation appear to be dissociable under a wide variety of circumstances.